Addition of Palbociclib to Fulvestrant Did Not Improve Progression-Free Survival Among Pre-Treated Patients With HR-Positive, HER2-Negative Metastatic Breast Cancer

Results from the phase 2 PACE study demonstrated that the addition of palbociclib to fulvestrant did not improve progression-free survival (PFS) compared to fulvestrant alone among patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who experienced disease progression after treatment with a CDK4/6 inhibitor plus an aromatase inhibitor.  

According to Erica L. Mayer, MD, MPH, Dana-Farber Cancer Institute, Boston, Massachusetts, and coauthors, “CDK 4/6 inhibitors are an important component of treatment for [HR]-positive/[HER2]- negative metastatic breast cancer, but it is not known if patients might derive benefit from continuation of CDK4/6 [inhibitors] with endocrine therapy beyond initial tumor progression or if the addition of checkpoint inhibitor therapy has value in this setting.”

In this open-label study, 220 patients with HR-positive, HER2-negative metastatic breast cancer who experienced disease progression on endocrine therapy (with an aromatase inhibitor or tamoxifen) and any CDK4/6 inhibitor after ≥12 months of exposure in the adjuvant setting were enrolled. Patients were randomized on a 1-to-2-to-1 basis to receive 500 mg of fulvestrant on days 1 and 15 in cycle 1 and again on day 1 of each subsequent monthly cycle (n = 55), fulvestrant plus 125 mg of palbociclib once daily on days 1 to 21 of each cycle (n = 111), or fulvestrant plus palbociclib and 10 mg/kg of once daily avelumab every 15 days (n = 54) in 28-day cycles until disease progression or relapse, unacceptable toxicity, withdrawal of consent, or death. The primary end point was PFS. Secondary end points included objective response rate (ORR), clinical benefit rate, and overall survival (OS). 

After a median follow-up of 23.6 months, the median PFS was 4.8 months in the fulvestrant arm, 4.6 months in the fulvestrant plus palbociclib arm (hazard ratio [HR], 1.11; 90% confidence interval [CI], 0.79 to 1.55; P = .62), and 8.1 months in the fulvestrant plus palbociclib and avelumab arm (HR, 0.75; 90% CI, 0.50 to 1.12; P = .23). The ORR was 7.3% in the fulvestrant arm, 9% in the fulvestrant plus palbociclib arm, and 13% in the fulvestrant plus palbociclib and avelumab arm. Clinical benefit rate was 29.1% in the fulvestrant arm, 32.4% in the fulvestrant plus palbociclib arm, and 35.2% in the fulvestrant plus palbociclib and avelumab arm. Median OS was 27.5 months, 24.6 months, and 42.5 months, respectively. 

Results demonstrated “that continuation of the same CDK4/6i beyond progression in combination with a change from [an aromatase inhibitor] to fulvestrant does not yield a PFS benefit compared with fulvestrant alone among patients with [HR]-positive/ [HER2-negative metastatic breast cancer],” concluded Dr Mayer et al. 

“Palbociclib should not be continued beyond progression,” added Journal of Clinical Oncology associate editor, Gini Fleming, MD, University of Chicago Medicine, Chicago, Illinois. “The trend toward benefit with the addition of avelumab is intriguing and should spur further research on the use of immune checkpoint inhibition in [HR]-positive breast cancer.” 

Source: 

Mayer EL, Ren Y, Wagle N, et al. PACE: A randomized phase II study of fulvestrant, palbociclib, and avelumab after progression on cyclin-dependent kinase 4/6 inhibitor and aromatase inhibitor for hormone receptor–positive/human epidermal growth factor receptor–negative metastatic breast cancer. J Clin Oncol. Published online: March 21, 2024. doi:10.1200/JCO.23.01940